Rheumatoid Arthritis

Overview

• Systemic disorder of unclear aetiology (Genetic and Environmental factors play a part)
• Chronic inflammation leads to joint destruction and deformity
• Early recognition and treatment crucial to limit progression as above
• Prevalence of 1% in whet populations, predominantly females in age 30-55 years
• Increased risk of CAD 

Genetic Factors:
Account for 50-65% of risk of developing RA
Shared Epitopes: HLA-DRB (DR4, DR14, DR1) are strong RFs
Polymorphisms including TNF alpha promoter PTPN22 and STAT 4

Hormonal Influence:

Risk reduced in women who have had children 

Further reduced by those who breast feed for a year or so

Disease activity subsides during pregnancy

Men have lower levels of androgenic hormones and higher level of estradiol

Environmental factors:

Smoking

Miners and Construction workers (?dust related)

Lower socio-economic groups

Diagnosis:

• Clinically a symmetrical polyarthropathy affecting small joints (MCP and PIP joints)
• Can be asymmetric and oligoarthritis 
• Associated Morning stiffness (>60mins)
• DIP and Lumbar spine spared usually
• Examination reveals soft boggy or fluctuant swelling and tenderness, with warmth and redness
• Reduced active and passive movement with active arthritis

Laboratory:

• Active inflammation: High CRP and ESR, Anaemia of chronic disease, High Plts, low albumin
• Synovial fluid analysis: High leucs (predominant neuts)
• RF present in 70% of patients
• Anti CCP present in 60% of patients
• ANA positive in 40% (non specific)
• Specificity of Anti CCP for RA is 95% when compared to RF which is 80%

Imaging:

• Xray reveals: Periarticular osteopenia, erosions, and symmetric joint space narrowing
• MRI shows bone marrow oedema and synovial proliferation as precursors to erosions

Extra-Articular manifestations:

• Constitutional: Fatigue, Weight loss
• Dermatologic: Rheum nodules, Ulcers, Vasculitis
• Opthalmolgic: Episcleritis, Scleritis, Keratoconjunctivitis sicca
• Haematologic: Aneamia of chronic disease, Thrombocytosis, Pancytopenia + splenomegally (Feltys), large granular lymphocyte syndrome
• Cardiovascular: premature CAD, chronic heart failure, pericarditis, secondary amyloidosis
• Pulmonary: Exudative Pleural effusion, Fibrosis, pulmonary nodules, BOOP, brochiectasis, cricoarytenoid disease producing stridor
• GI: Dry mouth
• Renal: Secondary amyloidosis
• Neuro: c1-c2 subluxation, Mononeuritis mulitplex, peripheral neuropathy

Treatment:

Aims are to reduce inflammation, maintain remission and preserve function

At each visit disease activity and damage needs assessing with questions about fatigue, weight loss, morning stiffness, joint pain, functional status and quantification with a scoring system, measurement of CRP/ESR, and imaging.

NSAIDs and Steroids Provide symptomatic relief but do not alter disease course.  Used PO and intrarticular DMARDs MTX Hydroxychloroquine Sulfasalazine Leflunomide Azathioprine Cyclophosphamide MMF Cyclosporine Immunosuppressive agents that slow and block autoimmune damage to joints. First line is MTX  Add on therapy of Hydroxy/sulfa in poorly controlled RA patients Biologic agents TNF alpha inhibitors (Etanercept, infliximab, adalimumab, golimumab, certolizumba pegol) T cell costimulation (Abatacept) Anti CD20 B cell depleting (Rituximab)  IL 6 receptor antagonist (Tocilizumab) Used if above therapies have failed. Prior to using all pts require: -       CXR -       Anti viral screen (HIV/Hep) -       TB screen -       Monitor for infections during treatment Live vaccines should be avoided in these patients Concurrent use of 2 or more biologics is not recommended Surgical Intervention Synovectomy Repair or tendon rupture Osteotomy for realignment  Joint fusion for stabilisation  Joint arthorplasty Specific concerns for RA patients: Pre op optimisation of FBC C Spine imaging  Risk of infection and bleeding post op Balancing risk of infection with immunosuppressive therapy and healing time Non pharmacological treatment: Patient education MDT approach: Phsyio/OT/Dietician Smoking cessation Yearly flu vaccine

Pericarditis

Classic findings:

1. Chest pain (sharp and severe) with pleuritic component
2. Pericardial Friction Rub hear on auscultation
3. Diffuse concave ST segment elevation on ECG, with PR segment depression
4. Pericardial effusion (present in 60% of patients)
5. Fever and elevated inflammatory markers

Worse in recumbent position

Differentials to consider: Acute MI, PE, Aortic dissection

Causes:

Idiopathic
- Presumed viral or autoimmune - 40% of all cases 

Infection
- Post viral: Coxsackie A and B, Echovirus, Adenovirus HIS, Hep B+C
- Bacterial - Staph, Strep, Haemophilus, pneumococcus
- Mycobacterium TB
- Fungi: Histoplasma, Aspergillus, Candida

Autoimmune
- Rheumatic disease: SLE, RA, scleroderma
- Others: UC, GCA, PAN

Radiation
- Thoracic radiation: occurs 5 months post exposure usually

Myocardial Infarction Related
- Acute MI - 1-3 days post acute MI (usually ST elevation type)
- Dressler Syndrome - occurs several weeks/months post MI

Neoplasm
- Lung/breast/lymphoma, leukaemia

Cardiac Injury
- After blunt and penetrating trauma: may develop tamponade
- Post pericardiotomy
- Iatrogenic: post catheter insertion

Medications
- Antiarrhythmics: Procainamide, amiodarone
- Antihypertensives: hydralazine
- Antibiotics: Penicillin
- Chemo: Doxorubicin, daunorubicin

Metabolic disorders
- Uraemic

Aortic disease
- Thoracic aortic pathology causing leaking or rupture into pericardial space

Other
- Radiofrequency catheter ablation of atrial fibrillation
- Takotsubo CM

Myopericarditis

• Occurs in 15% of patients with pericarditis
• ECG shows regional concave downward ST segment elevation
• ECHO shows new segmental or global left ventricular dysfunction
• Elevated cardiac markers

Treatment:

Identify and treat underlying cause if possible

Pain relief

Prevention of tamponade and constrictive pericarditis and recurrence

1) Aspirin or NSAIDs + PPI protection - Caution post MI (use aspirin as NSAIDs promote ventricular rupture). 

2) Colchicine added in refractory cases (COPE trial supports concurrent use with above from start)

3) Steroids

Cardiac Tumours

Primary

• 75% are benign; 25% are malignant
• Myxoma is the most common and 80% originate in the left atrium
• Other benign tumours include papillary fibroelastoma and lipoma
• Malignant tumours are sarcomas

Secondary

• Secondary tumours reach the heart by metastasis (primary usually lung and breast) or direct extension and are 20 times more common than primary tumours. 
• Renal, adrenal and liver cancers can invade via the IVC

Presentation
Usually vague with constitutional symptoms but can be dramatic including syncope, CVA, HB, VT and sudden death.

Investigations

TTE and TOE

CT and Cardiac MRI

Biopsy and surgically derived tissue for histology

Management

Myxoma should be surgically removed to reduce embolic events

Fibroelastomas should be excised is highly mobile

If surgical risk is high anti platelet or anticoagulation should be considered

Malignant tumours are not amenable to curative surgical excision

Heart Failure

Clinical syndrome characterised by dyspnea, effort intolerance, orthopnea, PND, nocturnal cough and oedema. Other symptoms include early satiety, N+V, abdo discomfort, wheezing, coughing, fatigue.

Signs:
- Elevated cardiac filling pressures and fluid overload
- Cardiac enlargement
- Reduced cardiac output
- Arrhythmia

NYHA classification
Class I                 No limitation on physical activity
Class II                Slight limitation on physical activity
Class III               Marked limitation on physical activity
- IIIa - symptoms with less than ordinary activity
- IIIb - symptoms with minimal exertion
Class IV              Unable to carry on any physical activity without symptoms

Medical Rx:

• ACE inhibitors
• Angiotensin receptor blockers
• Beta blockers
• Aldosterone antagonists
• Other vasodilators - hydralazine and isosorbide dinitrate

HF with preserved Ejection Fraction (HFPEF)
Often associated with uncontrolled HTN
RFs include older age, female, HTN, obesity, DM, CAD, CKD
Rx: ACE (perindopril), Beta blockers (Nebivolol), ARB (Candesartan, Irbesartan)

Biventricular Pacing (CRT) indications:
All of the following:

• NYHA class III or IV
• EF <= 35%
• Ventricular dyssynchroniy (QRS>= 120msec)

Aim is to restore myocardial electromechanical coupling and effective ventricular contraction
Combined ICD and CRT devices can be placed

Autoantibodies in Rheumatology

Autoantibody	Condition	Comments
ANA	SLE	Screening tool for Autoimmunity
Anti DS DNA	SLE	Correlates with Lupus disease activity esp kidney disease
Anti Smith	SLE	Most speicifc for SLE
Anti U1 RNP	MCTD, SLE	Higher titre seen in MCTD
Anti Ro/SSA, Anti LA/SSB	Sjogrens, RA, SLE, PSS	SICCA symptoms in SLE, associated with neonatal lupus
Anti SCL 70	Diffuse PSS	Pulmonary fibrosis more common
Anti centromere	Limited PSS (CREST)	Pulmonary HTN
c-ANCA (antiproteinase-3)	GPA
p-ANCA (antimyeloperoxidase)	MPA/ Churg strauss	Atypical p-ANCA seen in IBD
Anti Jo1	Myositis	ILD
RF	RA, Sjogrens, Cryoglobulinaemia	Antibody to Ig hence many false positives
Anti CCP	RA	Positive in 1/3rd RF negative patients
Anti histones	Drug induced SLE	Also seen in Native Lupus
Cryoglobulins	Vasculitis, hep C, myeloma, SLE, RA	Type 2 seen in cryoglobulinemic vasculitis

Tachycardia: Ventricular Arrhythmia

Premature Ventricular Contractions (PVCs)

• Occur in 75% of healthy individuals
• Pts report sensation of skipped beat or extra strong beat
• If no syncope, no structural heart disease or no FHx of sudden cardiac death then reassure!
• More common in HTN, LVH, HF, myocardial ischaemia, IHD. Rx with Beta blocker or Ca channel blocker, and Catheter ablation in those who fail medical Rx.

Ventricular Tachycardia with Structural Heart disease

• Rhythm greater than 100 BPM
• Originates in the ventricles
• Sustained if is lasts >30 secs or produces haemodynamic collapse
• Pts with previous MI or CM, VT usually monomorphic originating from small pathways of viable myocardium within scarred tissue
• SCD more common in those with poor EF, rapid VT, hypotension and syncope
• Rx: Beta blocker

In those with VF, haemodynamic unstable VT, or stable VT with structural heart disease ICDs are indicated. Amiodarone and Sotalol used as anti-arrhythmics to reduce ICD shock but do not reduce mortality. Catheter ablation for those with recurrent VT.

Idiopathic VT

• Usually provoked by exercise or emotional stress
• occurs more frequently in women than men in ages 20-40s
• Monomorphic and usually originates from RV outflow tract.
• ECG: runs of VT with LBBB pattern that is positive in inferior leads
• Differential: Arrhythmogenic right ventricular cardiomyopathy / Dysplasia (ARVC/D) which has epsilon waves 
• Treadmill test performed to see if provokes VT, and to look for ischaemia
• Echocardiogram done to look for structural abnormality
• Rx: Ca channel blockers, Beta blockers, class I or III antiarrhythmics, catheter ablation ( in order of preference)
• ICD NOT indicated

Ventricular Fibrillation (VF)

• Often the cause of sudden cardiac death
• Preceded by VT or ischaemic event usually
• ALS algorithm indicated and it is a SHOCKABLE rhythm
• Require ICD in the aftermath as part of secondary prevention

Tachycardia: Atrial Fibrillation

Atrial Fibrillation

• Rapid and uncoordinated electrical activity within the atria
• ECG: absence of P waves and irregular ventricular response
• Occurs in 10% of patients of patients over 80 years
• Associated with blood stasis in Left atrium, with clot formation and embolic event

Paroxysmal AF
- Self terminating AF
Persistent AF- Rhythm sustained for longer than 7 days
Permanent AF
- Continues AF and cardioversion has failed or it is no longer attempted
Lone AF
- AF occurring in the absence of structural heart disease in pt younger than 60 years

Associated with heart failure, hyperthyroidism, hypertension, WPW syndrome, cardiac surgery, myocardial infarction, myocarditis, pericarditis, acute pulmonary disease, mitral valve disease

Management:
- 12 lead ECG to capture rhythm and rate
- Blood tests: FBC, U+E, LFTs, TFTs
- Echocardiogram
- If no heamodynamic compromise anticoagulation and cardiovert within 3 weeks, and continue anticoagulation 4 weeks post cardioversion (goal INR 2.0-3.0)
- Use beta blockers. calcium channel blockers or digoxin to maintain R 60-100
- Emergency Cardioversion is indicated in those with hypertension, angina, heart failure or decreasing conscious level due to poor output.

Anticoagulation in AF

RISK factors for anticoagulation: Mitral stenosis, previous VTE, HF, systolic dysfunction, diabetes, HTN, mechanical heart valve and older age.

Chads2 score is used in patients without valvular disease to determine need and type of anticoagulation: - Low and intermediate risk can be treated with Aspirin alone.
- Those who are not candidates for warfarin can use CLOPIDOGREL and Aspirin but bleeding risk is higher and ti is inferior for preventing ischaemic CVA when compared to warfarin.
-

Newer Agents:
- Dagibatran

• Direct Thrombin inhibitor
• RE-LY trial showed Dagibatran to be superior to warfarin in preventing ischameic and haemorrhagic CVA, with reduced risk of life threatening bleeding but higher risk of GI bleeding.
• No lab monitoring required but no test can measure extent of anticoagulation
• No reversal agent available 

- Rivaroxaban / Apixaban

• Oral Factor Xa inhibitor
• Non inferior to warfarin for stroke prevention and demonstrates reduced risk of intracranial bleeding
• Risk of thrombotic event increased in first 28 days after it is stopped to bridging anticoagulation should be used

Non pharmacologic strategies:

• AF ablation - entails electrical isolation of the pulmonary veins so premature serial contractions can be stopped. Warfarin should be continued for 2-3 months post procedure, then CHADS2 score used to determine LT anticoagulation. 84% success rate. Complications include stroke, atrial oesophageal fistula, pulmonary vein stenosis, cardiac tamponade and death in 4.5% of patients.
• AV nodal Ablation
• Maze surgery - open cardiac surgery involving incisions and ablations of the right and left atria

Anti-Arrhythmics for Tachycardias

Anti Arrhythmic Medications

Vaughan Willaims Classification

	Mechanism of Action	Examples	Effect	Use
Class IA	Na channel blockade, some K channel block	Quinidine Procainamide Disopyramide	Slows conduction and prolongs repolarization	Preexcited AF, SVT, Ventricular arrhythmias
Class IB	Na channel blockade	Lidocaine Mexiletine Phenytoin	Slows conduction in diseased tissues, shortens repolarization	Ventricular arrhythmias
Class IC	Na channel blockade	Flecainide Propafenone	Markedly slows conduction. Slightly prolongs repolarization	AF, A flutter,
Class II	Beta blockade	Metoprolol Propranolol Atenolol	Suppresses automaticity and slows AV nodal conduction	Rate control of AF, SVT, ventricular arrhythmias
Class III	K channel blockade	Sotalol Amiodarone Dofetilide Dronedarone	Prolongs action potential duration	AF, ventricular arrhythmias
Class IV	Ca channel Blockade	Verapamil Diltiazem	Slows SA node automaticity and AV nodal conduction	SVT, rate control of atrial arrhythmias, triggered arrhythmias

USAGE:
- Avoid Class II and Class III in patients with decompensated heart failure and Wolff-Parkinson White syndrome
- Class I and III causes ventricular arrhythmias and Toxic
- Class IC (used for AF) should be avoided in those with CAD, IHD as increased risk of polymorphic VT. May also predispose to rapid 1:1 AV nodal conduction. therefore given with AV nodal blocker.
- Class III usually prolong QT interval, therefore increases risk of Torsades de pointes
- Amiodarone used in HF and LVH, but has several side effects: thyroid dysfunction, liver toxicity, pulmonary fibrosis and skin hypersensitivity
- Digoxin (MOA: Na-K exchange blocker and also increases vagal activity to heart) and Adenosine (MOA: Blocks A1 receptors in AV node) also included as anti-arrhythmics

Bradycardia

Heart Rate of <60 BPM

Symptoms:
Presyncope
Syncope
Fatigue
Dyspnoea
Exercise intolerance
Bradycardia included Ventricular arrhythmias

Sinus Node disease:
- Due to fibrotic replacement, ishaemic damage, post cardiac surgery, infiltrative causes (amyloid/sarcoid), increased vagal tone, medications including beta blockers ca channel blockers, genetic disease.
- Manifests asa sick sinus syndrome, sinus arrest or chronotropic incompetence

AV Node disease:
First degree HB
-Fixed prolonged PR (>200msecs)
Second degree HB
-Mobitz Type 1 (wenkebach)
-Type 2
Third degree HB

PPM insertion indications:
Symptomatic Bradycardia (HR <40) or sinus pauses
Symptomatic CHB or second degree HB (Type 1 or 2)
Asymptomatic HB or advanced second degree HB
AF with pauses >5 secs
Alternating Bundle branch block